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Safety and efficacy of S-1 in combination with carboplatin in non-small cell lung cancer patients with interstitial lung disease: a pilot study

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Abstract

Purpose

There is no established standard regimen for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). For them, we performed a pilot study to evaluate the feasibility of chemotherapy with carboplatin and S-1, which are known as cytotoxic drug with rare development of ILD as adverse event.

Methods

A total of 21 chemotherapy-naive NSCLC patients with ILD were prospectively enrolled between March 2009 and September 2011. Every 3 weeks, carboplatin at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered.

Results

The median age at initiating chemotherapy was 67. Histological examination revealed 10 patients (48 %) with adenocarcinoma. Before chemotherapy, partial pressure of arterial O2 (PaO2) was low with a median of 71 Torr on room air. The median number of cycles administered was four, and the overall response rate and disease control rate were 33 and 67 %, respectively. At the time of data cut-off, all patients were deceased. The median progression-free survival (PFS) and median overall survival (OS) periods were 4.2 and 9.7 months. There was no significant difference of PFS and OS according to tumor histology. Acute exacerbation (AE) of ILD following S-1 plus carboplatin occurred in two patients (10 %, 2/21) within first course treatment. However, they were successfully managed with steroid therapy and survived for 7.0 and 8.8 months, respectively, after AE-ILD development.

Conclusions

This is the first prospective study to evaluate the safety and efficacy of S-1 plus carboplatin treatment for NSCLC patients with ILD. This regimen could be a feasible option for NSCLC patients with ILD, regardless of tumor histology. Our results would support to carry out a large-scale clinical trial to confirm the feasibility of this regimen.

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References

  1. King TE Jr (2005) Clinical advances in the diagnosis and therapy of the interstitial lung diseases. Am J Respir Crit Care Med 172(3):268–279

    Article  PubMed  Google Scholar 

  2. Ozawa Y, Suda T, Naito T, Enomoto N, Hashimoto D, Fujisawa T, Nakamura Y, Inui N, Nakamura H, Chida K (2009) Cumulative incidence of and predictive factors for lung cancer in IPF. Respirology 14(5):723–728

    Article  PubMed  Google Scholar 

  3. Park J, Kim DS, Shim TS, Lim CM, Koh Y, Lee SD, Kim WS, Kim WD, Lee JS, Song KS (2001) Lung cancer in patients with idiopathic pulmonary fibrosis. Eur Respir J 17(6):1216–1219

    Article  CAS  PubMed  Google Scholar 

  4. Raghu G, Nyberg F, Morgan G (2004) The epidemiology of interstitial lung disease and its association with lung cancer. Br J Cancer 91(Suppl 2):S3–10

    Article  PubMed  PubMed Central  Google Scholar 

  5. Antoniou KM, Wells AU (2013) Acute exacerbations of idiopathic pulmonary fibrosis. Respir Int Rev Thorac Dis 86(4):265–274

    CAS  Google Scholar 

  6. Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr, Lasky JA, Loyd JE, Noth I, Olman MA, Raghu G, Roman J, Ryu JH, Zisman DA, Hunninghake GW, Colby TV, Egan JJ, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kondoh Y, Lynch DA, Muller-Quernheim J, Myers JL, Nicholson AG, Selman M, Toews GB, Wells AU, Martinez FJ, Idiopathic Pulmonary Fibrosis Clinical Research Network I (2007) Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 176(7):636–643

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kenmotsu H, Naito T, Mori K, Ko R, Ono A, Wakuda K, Imai H, Taira T, Murakami H, Endo M, Takahashi T (2015) Effect of platinum-based chemotherapy for non-small cell lung cancer patients with interstitial lung disease. Cancer Chemother Pharmacol 75(3):521–526

    Article  CAS  PubMed  Google Scholar 

  8. Kondoh Y, Taniguchi H, Kawabata Y, Yokoi T, Suzuki K, Takagi K (1993) Acute exacerbation in idiopathic pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases. Chest 103(6):1808–1812

    Article  CAS  PubMed  Google Scholar 

  9. Shimizu R, Fujimoto D, Kato R, Otoshi T, Kawamura T, Tamai K, Matsumoto T, Nagata K, Otsuka K, Nakagawa A, Otsuka K, Katakami N, Tomii K (2014) The safety and efficacy of paclitaxel and carboplatin with or without bevacizumab for treating patients with advanced nonsquamous non-small cell lung cancer with interstitial lung disease. Cancer Chemother Pharmacol 74(6):1159–1166

    Article  CAS  PubMed  Google Scholar 

  10. Shukuya T, Ishiwata T, Hara M, Muraki K, Shibayama R, Koyama R, Takahashi K (2010) Carboplatin plus weekly paclitaxel treatment in non-small cell lung cancer patients with interstitial lung disease. Anticancer Res 30(10):4357–4361

    CAS  PubMed  Google Scholar 

  11. Minegishi Y, Sudoh J, Kuribayasi H, Mizutani H, Seike M, Azuma A, Yoshimura A, Kudoh S, Gemma A (2011) The safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small cell lung cancer with idiopathic interstitial pneumonias. Lung Cancer 71(1):70–74

    Article  PubMed  Google Scholar 

  12. Enomoto Y, Kenmotsu H, Watanabe N, Baba T, Murakami H, Yoh K, Ogura T, Takahashi T, Goto K, Kato T (2015) Efficacy and safety of combined carboplatin, paclitaxel, and bevacizumab for patients with advanced non-squamous non-small cell lung cancer with pre-existing interstitial lung disease: a retrospective multi-institutional study. Anticancer Res 35(7):4259–4263

    CAS  PubMed  Google Scholar 

  13. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F (2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22(11):2184–2191

    Article  CAS  PubMed  Google Scholar 

  14. Okamoto I, Fukuoka M (2009) S-1: a new oral fluoropyrimidine in the treatment of patients with advanced non-small-cell lung cancer. Clin Lung Cancer 10(4):290–294

    Article  CAS  PubMed  Google Scholar 

  15. Takiuchi H, Ajani JA (1998) Uracil-tegafur in gastric carcinoma: a comprehensive review. J Clin Oncol 16(8):2877–2885

    CAS  PubMed  Google Scholar 

  16. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9(3):215–221

    Article  CAS  PubMed  Google Scholar 

  17. Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, Satoh T, Denda T, Ina K, Nishina T, Yamaguchi K, Takiuchi H, Esaki T, Tokunaga S, Kuwano H, Komatsu Y, Watanabe M, Hyodo I, Morita S, Sugihara K (2010) Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol 11(9):853–860

    Article  CAS  PubMed  Google Scholar 

  18. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K, Group A-G (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357(18):1810–1820

    Article  CAS  PubMed  Google Scholar 

  19. Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M (2013) Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 31(13):1640–1648

    Article  CAS  PubMed  Google Scholar 

  20. Yamada Y, Takahari D, Matsumoto H, Baba H, Nakamura M, Yoshida K, Yoshida M, Iwamoto S, Shimada K, Komatsu Y, Sasaki Y, Satoh T, Takahashi K, Mishima H, Muro K, Watanabe M, Sakata Y, Morita S, Shimada Y, Sugihara K (2013) Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 14(13):1278–1286

    Article  CAS  PubMed  Google Scholar 

  21. Trisolini R, Lazzari Agli L, Tassinari D, Rondelli D, Cancellieri A, Patelli M, Falcone F, Poletti V (2001) Acute lung injury associated with 5-fluorouracil and oxaliplatinum combined chemotherapy. Eur Respir J 18(1):243–245

    CAS  PubMed  Google Scholar 

  22. Kurakawa E, Kasuga I, Ishizuka S, Yoshida T, Kunisawa A, Minemura K, Utsumi K, Ohyashiki K (2001) Interstitial pneumonia possibly due to a novel anticancer drug, TS-1: first case report. Jpn J Clin Oncol 31(6):284–286

    Article  CAS  PubMed  Google Scholar 

  23. Shitara K, Munakata M, Koizumi W, Sakata Y (2007) A case of suspected S-1 induced interstitial pneumonia. Gan to kagaku ryoho Cancer Chemother 34(4):619–622

    Google Scholar 

  24. Tada Y, Takiguchi Y, Fujikawa A, Kitamura A, Kurosu K, Hiroshima K, Sakao S, Kasahara Y, Tanabe N, Tatsumi K, Kuriyama T (2007) Pulmonary toxicity by a cytotoxic agent, S-1. Intern Med 46(15):1243–1246

    Article  PubMed  Google Scholar 

  25. Ueyama Y, Yamamoto D, Yoshida H, Kanematsu S, Nakatake R, Kasahara N, Tanaka K, Shoji T, Okukawa H, Kwon AH (2010) A case of interstitial pneumonitis induced by S-1. Gan to kagaku ryoho Cancer Chemother 37(8):1603–1606

    Google Scholar 

  26. Yamamoto N, Ohshima T, Sato T, Makino H, Kanazawa A, Yamada T, Murakami H, Yukawa N, Nagano Y, Fujii S, Kunisaki C, Tsukahara T, Rino Y, Masuda M, Imada T (2008) A case of interstitial pneumonia after S-1 administration for gastric cancer. Gan to kagaku ryoho Cancer Chemother 35(11):1935–1937

    Google Scholar 

  27. Yamane H, Kinugawa M, Umemura S, Shiote Y, Kudo K, Suwaki T, Kamei H, Takigawa N, Kiura K (2011) An oral fluoropyrimidine agent S-1 induced interstitial lung disease: a case report. World J Clin Oncol 2(7):299–302

    Article  PubMed  PubMed Central  Google Scholar 

  28. Okamoto I, Yoshioka H, Morita S, Ando M, Takeda K, Seto T, Yamamoto N, Saka H, Asami K, Hirashima T, Kudoh S, Satouchi M, Ikeda N, Iwamoto Y, Sawa T, Miyazaki M, Tamura K, Kurata T, Fukuoka M, Nakagawa K (2010) Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer: results of a west Japan oncology group study. J Clin Oncol 28(36):5240–5246

    Article  CAS  PubMed  Google Scholar 

  29. Yoshioka H, Okamoto I, Morita S, Ando M, Takeda K, Seto T, Yamamoto N, Saka H, Atagi S, Hirashima T, Kudoh S, Satouchi M, Ikeda N, Iwamoto Y, Sawa T, Nakanishi Y, Nakagawa K (2013) Efficacy and safety analysis according to histology for S-1 in combination with carboplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer: updated results of the West Japan Oncology Group LETS study. Ann Oncol 24(5):1326–1331

    Article  CAS  PubMed  Google Scholar 

  30. Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M (2007) Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol 18(2):317–323

    Article  CAS  PubMed  Google Scholar 

  31. Chiyo M, Sekine Y, Iwata T, Tatsumi K, Yasufuku K, Iyoda A, Otsuji M, Yoshida S, Shibuya K, Iizasa T, Saitoh Y, Fujisawa T (2003) Impact of interstitial lung disease on surgical morbidity and mortality for lung cancer: analyses of short-term and long-term outcomes. J Thorac Cardiovasc Surg 126(4):1141–1146

    Article  PubMed  Google Scholar 

  32. Miyazaki K, Satoh H, Kurishima K, Nakamura R, Ishikawa H, Kagohashi K, Hizawa N (2010) Interstitial lung disease in patients with small cell lung cancer. Med Oncol 27(3):763–767

    Article  PubMed  Google Scholar 

  33. American Thoracic S, European Respiratory S (2002) American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 165(2):277–304

    Article  Google Scholar 

  34. Lynch DA, Godwin JD, Safrin S, Starko KM, Hormel P, Brown KK, Raghu G, King TE Jr, Bradford WZ, Schwartz DA, Webb WR, Idiopathic Pulmonary Fibrosis Study G (2005) High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med 172(4):488–493

    Article  PubMed  Google Scholar 

  35. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247

    Article  CAS  PubMed  Google Scholar 

  36. Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, Taguchi Y, Nagai S, Itoh H, Ohi M, Sato A, Kudoh S (2005) Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 171(9):1040–1047

    Article  PubMed  Google Scholar 

  37. Agarwal R, Jindal SK (2008) Acute exacerbation of idiopathic pulmonary fibrosis: a systematic review. Eur J Intern Med 19(4):227–235

    Article  PubMed  Google Scholar 

  38. Ito K, Jin Z (2015) Characteristics of and risk factors for interstitial pneumonia due to TS-1(R) capsule administration-case reviews from a drug use results survey on non-small cell lung cancer patients and spontaneous reports. Gan to kagaku ryoho Cancer Chemother 42(5):595–603

    Google Scholar 

  39. Isobe K, Hata Y, Sakamoto S, Takai Y, Shibuya K, Homma S (2010) Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti-cancer therapy. Respirology 15(1):88–92

    Article  PubMed  Google Scholar 

  40. Kenmotsu H, Naito T, Kimura M, Ono A, Shukuya T, Nakamura Y, Tsuya A, Kaira K, Murakami H, Takahashi T, Endo M, Yamamoto N (2011) The risk of cytotoxic chemotherapy-related exacerbation of interstitial lung disease with lung cancer. J Thorac Oncol 6(7):1242–1246

    Article  PubMed  Google Scholar 

  41. Tamiya A, Naito T, Miura S, Morii S, Tsuya A, Nakamura Y, Kaira K, Murakami H, Takahashi T, Yamamoto N, Endo M (2012) Interstitial lung disease associated with docetaxel in patients with advanced non-small cell lung cancer. Anticancer Res 32(3):1103–1106

    PubMed  Google Scholar 

  42. Watanabe N, Niho S, Kirita K, Umemura S, Matsumoto S, Yoh K, Ohmatsu H, Goto K (2015) Second-line docetaxel for patients with platinum-refractory advanced non-small cell lung cancer and interstitial pneumonia. Cancer Chemother Pharmacol 76(1):69–74

    Article  CAS  PubMed  Google Scholar 

  43. Kim DS, Park JH, Park BK, Lee JS, Nicholson AG, Colby T (2006) Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features. Eur Respir J 27(1):143–150

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan

    Akimasa Sekine, Tomohisa Baba, Satoshi Ikeda, Ryo Okuda, Takeshi Shinohara, Shigeru Komatsu, Eri Hagiwara, Takashi Ogura & Terufumi Kato

  2. Department of Internal Medicine, Mito Medical Center, University of Tsukuba, Tsukuba, Japan

    Hiroaki Satoh

  3. Department of Radiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan

    Tae Iwasawa

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  1. Akimasa Sekine
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  2. Hiroaki Satoh
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  3. Tomohisa Baba
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  4. Satoshi Ikeda
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Correspondence to Akimasa Sekine or Terufumi Kato.

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Conflict of interest

Dr. Kato has received lecture fees from AstraZeneca, Boehringer Ingelheim, and Chugai Pharmaceuticals and research support from Boehringer Ingelheim and Chugai Pharmaceuticals. None of the remaining authors have any conflict of interest to declare.

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Sekine, A., Satoh, H., Baba, T. et al. Safety and efficacy of S-1 in combination with carboplatin in non-small cell lung cancer patients with interstitial lung disease: a pilot study. Cancer Chemother Pharmacol 77, 1245–1252 (2016). https://doi.org/10.1007/s00280-016-3040-8

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